Effect of hypoglycemia on amino acid and protein metabolism in healthy humans.

Abstract

In response to hypoglycemia, healthy individuals rapidly antagonize insulin action on glucose and lipid metabolism, but the effects on protein metabolism are unclear. Because amino acids are an important substrate for gluconeogenesis and a fuel alternative to glucose for oxidation, we evaluated whether hypoglycemia antagonizes the hypoaminoacidemic and the antiproteolytic effects of insulin and changes the de novo synthesis of glutamine, a gluconeogenic amino acid. To this purpose, in 7 healthy subjects, we performed 2 studies, 3.5 h each, at similar insulin but different glucose concentrations (i.e., 4.9 ± 0.1 mmol/l [euglycemic clamp] or 2.9 ± 0.2 mmol/l [hypoglycemic clamp]). As expected, hypoglycemia antagonized the insulin suppression of glucose production achieved in euglycemia (from 21 ± 15 to 116 ± 12% of basal, P < 0.001), the stimulation of glucose uptake (from 207 ± 28 to 103 ± 7% of basal, P < 0.01) and the suppression of circulating free fatty acids (from 30 ± 5 to 80 ± 17% of basal, P < 0.001). In contrast, hypoglycemia increased the insulin suppression of circulating leucine (from 63 ± 1 to 46 ± 2% of basal, P < 0.001) and phenylalanine (from 79 ± 3 to 64 ± 3% of basal, P < 0.001) concentrations. Hypoglycemia did not change the insulin suppression of proteolysis (from 79 ± 2 to 82 ± 4% of basal, P < 0.001). However, hypoglycemia doubled the insulin suppression of the glutamine concentrations (from 84 ± 3 to 63 ± 3% of basal, P < 0.01) in the absence of significant changes in the glutamine rate of appearance, but it also caused an imbalance between glutamine uptake and release. This study demonstrates that successful counterregulation does not affect proteolysis. Moreover, it does not increase the availability of circulating amino acids by de novo synthesis. In contrast, despite the lower concentration of circulating amino acids, hypoglycemia increases the uptake of glutamine that can be used for gluconeogenesis and as a fuel alternative to glucose.

Insulin sensitivity of protein and glucose metabolism in overweight female adolescents with type 1 diabetes mellitus: positive modulation by physical exercise

“…This study showed that, in females, the association of type 1 DM, overweight and young age increases strikingly the insulin resistance of glucose metabolism. This conclusion is based on the comparison of the present findings with those previously reported by us using the same experimental protocol, in healthy young adult type 1 diabetic subjects [3,12,13], and in lean and obese young adults [14], and by other authors who have studied healthy and diabetic adolescents of both sexes [15].…”

“…Endogenous leucine flux was calculated as previously described [12] on the basis of [ 13 C]leucine enrichment values in the last 60 minutes of the basal and the hyperinsulinemic periods.…”

Nonhepatic glucose production in humans

“…The glucose concentration diminished during that period of time, but it did so at a rate that was very slow compared with what we would have expected if the glucose production had been consistently reduced with the liver removal. The decrement in circulating glucose was only 15%/h, whereas we previously found that it decreased by 30-40% within 30 min during hypoglycemic clamp studies in which the glucose production was reduced by 50% and the glucose disappearance was not appreciably changed (1,4). This slow reduction in circulating glucose during the anhepatic phase might have occurred either because of a substantially maintained glucose production or because of a markedly decreased glucose uptake.…”

“…Plasma amino acid concentrations and enrichments were measured by electron impact GC-MS. Before derivatization, amino acids were isolated from plasma by use of cation-exchange columns as previously described (1). Amino acids eluted from the columns were evaporated to dryness and derivatized to form the tert-butyldimethylsilyl (TBDMS) derivative.…”

“…All plasma and serum aliquots were frozen at Ϫ60°C until later analysis. (1). Injections of the samples were made into a GC-MS instrument (model 5970; HewlettPackard, Palo Alto, CA) operated by electron impact ionization as previously described.…”